A team from the Hospital Clínic-IDIBAPS has led a pioneering study that looks deeper into molecular alterations of the brain in patients with anti-NMDAR encephalitis and compares them with those observed in schizophrenia. These two diseases can present with psychotic and cognitive symptoms in a similar way, although the current clinical approaches are very different. The study, published in Biological Psychiatry, contributes to a better understanding of the mechanisms that both disorders share and of the differences that allow them to be distinguished from each other, opening the door to improvement of diagnosis and treatment for these patients.
The study has been carried out by the Multimodal neuroimaging in early and high-risk psychosis group led by Gisela Sugranyes in collaboration with the Pathogenesis of autoimmune neuronal disorders led by Josep Dalmau and the Child and adolescent psychiatry and psychology group led by Josefina Castro-Fornieles, all three within the context of the IDIBAPS Synaptic autoimmunity in neurology, psychiatry and cognitive neuroscience programme. The study includes the follow-up of 32 patients in the post-acute phase of anti-NMDAR encephalitis, 27 people with schizophrenia, and 36 healthy controls over 24 months. Using magnetic resonance spectroscopy, the researchers measured several metabolites related to neuronal and glial function, such as glutamate, myo-inositol and N-acetyl-aspartate + N-acetyl-aspartate-glutamate (NAAG).
Differences in glutamate levels
The results show that patients with anti-NMDAR encephalitis have significantly lower levels of glutamate and derived metabolites in the prefrontal cortex during the recovery phase of the disease than people with schizophrenia and healthy controls. This suggests that the disease leaves a prolonged imprint on brain circuits regulated by NMDA receptors, despite clinical improvement.
Inflammatory processes common to both disorders
As well as differences, the research identifies significant similarities. Both patients with anti-NMDAR encephalitis and people with schizophrenia have high levels of myo-inositol, a marker linked to neuroinflammation processes. This result indicates that the two disorders share an inflammatory component, although they have different causes and different clinical courses.
According to Gisela Sugranyes, senior author of the article: “This work reinforces the idea that the study of anti-NMDAR encephalitis, through brain magnetic resonance imaging, can help us better understand the molecular changes related to NMDA receptor disfunction, which is currently considered a key mechanism in the origin of schizophrenia symptoms”.
Moreover, NAAG values, considered an indicator of neuronal integrity, do not show significant differences between any of the groups, suggesting that there is no significant permanent neuronal damage. As highlighted by Adriana Fortea and Maria Ortuño, researchers at IDIBAPS and first authors of the article: “The results reinforce the idea that encephalitis is a reversible disease and that, despite leaving persistent alterations, it does not cause severe neuronal loss.”
Clinical implications and future lines of research
The research provides new insights into the post-acute phase of anti-NMDAR encephalitis, a phase that has often been considered solely as recovery, but which, according to the researchers, still presents active alterations in brain metabolism. This knowledge can help professionals to design more appropriate follow-up strategies and implement personalised cognitive rehabilitation programmes that take into account the molecular particularities of each disorder.
